Home-based circuit training improves blood lipid profile, liver function, musculoskeletal fitness, and health-related quality of life in overweight/obese older adult patients with knee osteoarthritis and type 2 diabetes: a randomized controlled trial during the COVID-19 pandemic

Background There is strong evidence showing the association between obesity, type 2 diabetes mellitus (T2DM), and knee pain resulting from osteoarthritis. Regular exercise has been reported as a foundational piece of the preventive therapy puzzle for knee osteoarthritis (KOA) patients. Nonetheless, evidence-based exercise protocols for people with comorbidities, such as obesity, T2DM, and KOA are limited. Therefore, the present trial aimed to assess the effectiveness of a 12-week home-based circuit training (HBCT) protocol on various indices related to cardiometabolic health, musculoskeletal fitness, and health-related quality of life (HRQoL) among overweight/obese older adult patients with KOA and T2DM during the COVID-19 lockdown. Methods This is a randomized controlled trial study registered at the National Medical Research Register (ID: RSCH ID-21-01180-KGTNMRR ID-21-02367-FUM) and obtained approval on December 9, 2021. Seventy overweight or obese patients with KOA and T2DM (62.2 ± 6.1 years; 56% female) were randomly assigned to the intervention group (n = 35, HBCT) or the no-exercise control group (n = 35, CON). HBCT performed a 12-week progressive protocol (seven exercises; 15–30 repetitions per exercise, 1 min passive rest between exercises; 2–4 rounds per session; 20–60 min total session duration). Blood samples were collected, and assays were performed to assess the lipid profile, liver function, and fasting blood glucose (FBG). In addition, the 30-s Chair Stand Test (30CST) was used to evaluate lower body muscular strength and endurance while the Timed Up and Go (TUG) test was used to evaluate lower limb function, mobility, and the risk of falls for all the participants. HRQoL was assessed using the Osteoarthritis Knee and Hip Quality of Life (OAKHQoL). All the assessments were conducted at pre-, mid-, and post-training stages during the application or practice of the exercise protocol, rather than during the training sessions themselves. Results HBCT significantly reduced total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), aminotransferase, alanine aminotransferase, FBG and knee pain (p < 0.05). Furthermore, HBCT induced meaningful increases in high-density lipoprotein (HDL-C), lower body muscular strength, endurance, function, mobility, and HRQoL in overweight/obese older adults with T2DM and KOA (p < 0.05). Conclusion The present outcomes recommend that an injury-free HBCT program may improve various indicators related to cardiometabolic health, musculoskeletal fitness, and HRQoL in elderly with overweight/obesity, T2DM and KOA. These findings offer valuable insights for clinicians and practitioners seeking evidence-based exercise interventions tailored for patients managing substantial metabolic and musculoskeletal health challenges in clinical practice.


Introduction
The global healthcare systems are significantly influenced by the pervasive presence of obesity and its adverse effects [1].Since 1980, the prevalence of obesity has shown a notable rise, as indicated by the extensive examination of data from 195 countries conducted by the Worldwide Burden of Disease research [2,3].The rise in obesity rates worldwide has been accompanied by a corresponding surge in the occurrence of type 2 diabetes mellitus (T2DM) [2,3].Interestingly, several studies have demonstrated a correlation between the deterioration of knee pain and the existence of one or multiple comorbid conditions, including obesity and T2DM [4][5][6].
It is worth mentioning that a unit increase in body mass index (BMI) can elevate the likelihood of developing knee osteoarthritis (KOA) by 15% [7].Strong evidence shows a high correlation between T2DM and KOA [8,9], and this correlation has been linked to lower levels of physical activity and self-efficacy for strength training [10].One of the primary underlying mechanisms causing KOA in T2DM patients is assumed to be the increased mechanical strain on weight-bearing joints, particularly the knees since both diseases share overweight and obesity as significant shared risk factors.Compared to non-diabetic adults, patients with T2DM and KOA often have poorer muscular strength and lower leg skeletal mass [11,12], and the impaired muscular function may result in insulin resistance [13,14].Importantly, the literature also implies that quadriceps strength is crucial for comprehending the variety and importance of the results of a 30-s chair stand test (30CST) [15].Improving a measure of lower limb strength is one of the primary drivers behind persons with chronic, acute, and devastating KOA seeking exercise is an improvement in leg strength and endurance, lower limb function, and mobility [16][17][18].
Engaging in regular exercise enhances both muscle strength and mass [19], as well as reducing the levels of inflammatory cytokines and providing protection to the knee joint [20].According to a prior investigation by Juhl et al. (2014), the most effective exercise regimens for treating patients with KOA should prioritize lower limb functionality and cardiovascular endurance.However, Bennell, Hinman [21] suggested that an effective strategy for managing the various complexities associated with OA consists of integrating both resistance and aerobic exercise, which also seems as one of the most popular and beneficial types of exercise for improving numerous cardiometabolic health and musculoskeletal fitness markers among individuals with a BMI ≥ 25 kg/m 2 [22][23][24][25][26][27][28][29].However, individuals with excessive weight demonstrate low adherence and high attrition rates to movement-based programs due to BMI perception and body image dissatisfaction related to poor functional capacity as well as impaired musculoskeletal and mental health [30,31].
Circuit training (CT) is an effective training program for improving cardiorespiratory and musculoskeletal fitness, including a group of muscle-strengthening exercises of all the major muscle groups that are completed consecutively with minimal or no rest intervals.Also, aerobic-based exercises can be included, which has potential benefits for various chronic diseases, including KOA [32].In this training program, each exercise is performed for a specified number of repetitions or for a set time seconds before a brief rest and moving onto the next exercise and therefore the participants' heart rate can be elevated throughout the workout [33,34].Such exercises; 15-30 repetitions per exercise, 1 min passive rest between exercises; 2-4 rounds per session; 20-60 min total session duration).Blood samples were collected, and assays were performed to assess the lipid profile, liver function, and fasting blood glucose (FBG).In addition, the 30-s Chair Stand Test (30CST) was used to evaluate lower body muscular strength and endurance while the Timed Up and Go (TUG) test was used to evaluate lower limb function, mobility, and the risk of falls for all the participants.HRQoL was assessed using the Osteoarthritis Knee and Hip Quality of Life (OAKHQoL).All the assessments were conducted at pre-, mid-, and post-training stages during the application or practice of the exercise protocol, rather than during the training sessions themselves.
a workout structure requires shorter rest periods compared to traditional strength training, resulting in significantly reduced overall workout time [35,36] while considering attractive in the global exercise community [37].
Despite the positive exercise training-induced adaptations, the most effective exercise approach for patients with obesity, T2DM, and KOA is currently unclear.Thus, this pragmatic randomized controlled trial was conducted in a home-based setting, aiming to primarily assess the efficacy of a 3-month home-based circuit training (HBCT) protocol on (i) lipid homeostasis, (ii) liver function, (iii) fasting blood glucose (FBG), and (iv) musculoskeletal fitness among sedentary overweight/ obese older adult patients with KOA and T2DM.The hypothesis posited that the intervention group (HBCT) would induce more pronounced positive changes in comparison to the control group (CON).
The study was conducted at the Physiology Laboratory of the School of Medical Sciences at the University Sains Malaysia (USM) from September 13, 2021 until September 12, 2022.Ethical approval was obtained from the Human Research Ethics Committee of USM before the commencement of the study (approval code: JEPeM 21,050,374).This study adhered to the CONSORT guidelines.Initially, 162 patients were approached via posters distributed in the Orthopedics Clinic at USM Hospital and were screened by phone.Of these, 70 met the inclusion criteria and were randomly recruited into the study.Pre-training assessments were conducted before the randomization to determine participants' eligibility.Written informed consent was obtained from all participants prior to the study.Patients were randomly divided into two groups through a computer-generated random allocation sequence, conducted independently by a statistician using simple randomization (http:/www.randomization.com).Additionally, the statistician was blinded and remained unaware of the group's allocation.Similarly, the assessors were kept blinded, with no knowledge of both the study objectives and the random allocation of patients to different study groups throughout the entire process.

Participants
The sample size for this study was calculated based on repeated measure ANOVA within-between factors using a preliminary power analysis (G*Power 3.1.9.2) with type I error of 0.05, power of study 80%, number of groups of 2, number of measurements of 3, a medium effect-size of 0.25 correlation between the repeated measures of 0.5, non-sphericity correction ε of 1, and considering a dropout of 20% as reported in previous training studies with overweight/obese individuals investigating similar outcome measures [23,26,28,29,31,38].A total of 35 participants in each group were required for this study.This study involved 70 patients meeting the inclusion criteria as follows: (i) age > 55 years, (ii) diagnosed with KOA with Kellgren-Lawrence criteria grades 2 and 3, indicating moderate KOA, which was based on radiological assessments conducted by a traumatologist, (iii) two and three KOA (unilateral or bilateral), (iv) chronic knee pain for more than three months, (v) T2DM based on fasting plasma glucose > 7.0 mmol•L-1 and glycated hemoglobin (HbA1c) > 6.5%, (vi) overweight or obesity (BMI ≥ 25 kg/m 2 ), (vii) receiving the standard treatment (all patients were taking diabetes medications), and (viii) providing a certificate of a negative COVID-19 diagnostic test (PCR or rapid test).Patients were excluded from the study if during the intervention they demonstrated (i) secondary KOA, (ii) acute knee pain, (iii) changes in medication, supplementation, and/or diet, (iv) changes in habitual physical activity, (v) intraarticular hyaluronic acid injection treatment within one year, (vi) smoking, (vii) dementia or any psychiatric diseases, (viii) adherence to less than 90% of the total prescribed exercise sessions, or (ix) they tested positive for COVID-19.The Charlson Comorbidity Score (CCS) was used to evaluate patients' health status, examining 17 chronic diseases with assigned weighted scores or values index [39].Patients' CCS was used to group the comorbidity into the following groups: 0: none, 1-2: mild, 3-4: moderate, and ≥ 5: severe [40,41].Following the provision of informed written consent, patients were instructed to abstain from any additional forms of exercise and to uphold their prevailing habitual physical activity levels and dietary patterns over a 3-month intervention period.Consequently, participants' logbooks were scrutinized at each visit to verify the absence of alterations in nutritional behavior and physical activity patterns.CON group followed standard treatment (diabetes medications) without engaging in any structured exercise throughout the intervention.Table 1 shows participants' characteristics.

Exercise protocol
Patients were encouraged not to change their habitual physical activity levels during the study.Any deviation from the protocol was considered a reason for exclusion.
During regular follow-up, participants were asked whether they had engaged in any activity that might be interpreted as interference with the intervention.Participants in the exercise group performed HBCT training three times per week on non-consecutive days for 12 weeks.However, the first session was conducted at USM Hospital and participants were instructed how to perform the prescribed exercises in a correct form.The HBCT protocol was adapted from a previous study [42] and is shown in Fig. 2. Progressive overloading was applied for the safety of participants, since they were sedentary overweight/obese adults with KOA and T2DM as well as to allow continuous progress to occur.In each session, participants performed seven exercises (two aerobic-and five resistance-based) in a circuit fashion, using bodyweight movements and adjustable dumbbells for varied weights, activating all the major muscle groups.
In weeks 1-6, participants executed 15 repetitions for 2 rounds with 1 min passive rest between exercises and rounds.In weeks 7-12, participants executed 30 repetitions for 4 rounds with the same rest as prescribed in weeks 1-6.Each round lasted 10-15 min and the total session duration was 20-60 min, aiming to help participants adapt gradually to increasing training volume.Such an exercise programming approach aimed to limit potential training-related injuries, overreaching and overtraining while providing an engaging and inclusive exercise experience in a real-world setting.A tutorial video was developed and provided to participants to ensure a correct demonstration of all prescribed exercise techniques with proper form at a controlled, moderate speed.For resistance-based exercises, participants were encouraged to use a comfortable weight at the beginning of the study and progressed to heavier weights that allowed them to complete the prescribed number of repetitions at each exercise station.A 5-min warm-up and a 5-min cool-down period were applied in all sessions.The rate of perceived exertion (RPE) was self-recorded using the Borg scale ranging from 6 (rest) to 20 (maximal) [43].RPE values were recorded for each round and mean exertion was calculated.Participants were advised to adjust the magnitude of their effort progressively during the 12-week intervention (weeks 1-6: RPE 11-13; weeks 7-12: RPE 14-16).A logbook was given to the participants to record their adherence to the prescribed exercise sessions and the RPE values per session.The logbook was checked through weekly follow-up via telephone calls and during each visit.Furthermore, a text message was sent to HBCT patients on a weekly basis regarding inquiries about the exercise routine.

Assessment procedures
All patients were instructed to avoid consuming caffeinated beverages and strenuous exercise 24 h before the first visit.A total of three visits were performed and all outcomes were assessed through the three visits (baseline, weeks 6 and 12) in the morning (07:00-09:00 a.m.) after an overnight fast (Fig. 3).All measurements were performed at USM Hospital.During the first visit (baseline), assessments were carried out for body mass index (BMI), FBG, lipid profile, liver function parameters as well as the level of pain using Visual Analogue Scale (VAS) score.Comorbidity was assessed using the Charlson Comorbidity Score [41].In addition, the 30-s Chair Stand Test (30CST) was used to evaluate lower body muscular strength and endurance while the Timed Up and Go (TUG) test was used to evaluate lower limb function, mobility, and the risk of falls for all the participants.Health-related quality of Life (HRQoL) was assessed using the Osteoarthritis Knee and Hip Quality of Life (OAKHQoL).During the second (mid-testing) and third (post-testing) visits at week 6 and 12, respectively, similar assessments to those conducted at baseline were carried out, except for biomarkers that were not assessed at week 6.They were not given access to the randomization sequence.Similarly, the statistician responsible for data analysis was also blinded and unaware of the group allocation.

Biomarkers
Blood samples and assays were carried out according to standard procedures as previously described [28].In brief, the blood samples (10 ml) were drawn from the participants after 12 h of fasting, put into a heparinized sterile tube, and kept on ice until processing.The blood was centrifuged at 1500 rpm for 15 min at 4 °C.The separated serum was stored at − 80 °C until further analysis.Commercially available kits (Human) were used for measuring TG (#10,724), TC (#10,028), and HDL (#10,018) on an automated clinical chemistry analyzer HumaStar 200 (Human Diagnostics, Wiesbaden, Germany).FBG was determined using a commercially available ELISA kit (#KA4088, Abnova Corporation, Taipei, Taiwan) as previously reported [28].Low-density lipoprotein cholesterol (LDL-C) concentration was calculated according to the equation LDL = TC − HDL − (TG / 5) [44].All assays were performed in duplicates on the same day.The interand intra-assay coefficients of variability for all assays ranged from 6.1 to 10.8%, 5.3-9.7%, and from 4.9 to 8.6%, respectively.

Musculoskeletal fitness
The 30CST and the TUG tests were administered to the participants under the supervision of assessors who provided standard instructions.During the 30CST, participants began in a seated position, and upon the command "go, " they repeatedly stood up and sat down as quickly as possible for 30 s.The assessors recorded the total number of repetitions completed by the participants as the standard clinical outcome for the 30CST [45].On the other hand, during the TUG test, participants started in a seated position on a chair.Following the command "go, " they rose from the chair, walked three meters comfortably and safely, made a 180° turn, returned to the chair, and sat down again.The assessors used a stopwatch to record the total time taken to perform the TUG test as the standard clinical outcome for this assessment [46].

Health-related quality of life
The osteoarthritis knee and hip quality of life (OAKHQoL) questionnaire was used as a validated tool to assess how KOA specifically affects the HRQoL of participants [47].This questionnaire considers specific criteria relevant to the HRQoL of individuals with KOA, such as social support, sleep, medication side effects, feelings of embarrassment, use of public transportation, difficulty in movement after prolonged stillness, and sexuality.It comprises 31 items categorized into five domains: physical activity, pain, mental health, social function, and social support.The preliminary testing showed the reliability of the five dimensions to be satisfactory (intraclass correlation coefficients: 0.70-0.85).Each item within the domains was assessed on a numerical rating scale from 0 to 10.The final scores were calculated as the average of all the item scores within their respective domains, ranging from 0 to 10 [48].

Pain
A 100-mm horizontal VAS was employed to assess pain levels.The pain VAS was defined as painless on the left and worst pain on the right of the horizontal scale.
Following a comprehensive explanation of how to effectively utilize the pain VAS, participants were instructed to independently mark their perceived level of pain on the scale.The resulting pain VAS score was subsequently determined by measuring the distance in millimeters from the leftmost point of the scale to the participant's marked location [49].

Statistical analysis
The Shapiro-Wilk test was used to verify data normality.Participants' baseline characteristics were compared using an independent t-test for normally distributed data and the Mann-Whitney test for not normally distributed data.A mixed ANOVA model with a simple main effect analysis of time/group was applied to give estimates based on group and time, and detect between time points across the groups.Effect sizes were calculated using eta squared (η 2 ) and were interpreted as small, mediumsized, and large for values 0.01-0.05,0.06-0.13,and ≥ 0.14, respectively [50].A value of p < 0.05 was considered to be statistically significant.Statistical analysis was carried out using the SPSS 27.0 software (IBM Corp., Armonk, NY, USA).Results were presented as mean difference (MD), 95% confidence intervals (CI), η 2 and p values.
The remaining three exclusions (0.3%) were due to other reasons, such as family and work commitments.Therefore, a total of 69 participants (HBCT, n = 34; CON, n = 35) completed the study and the attendance rate for HBCT was 91.7% (Fig. 1).One patient in HBCT dropped out due to loss of follow-up (dropout rate: 1.4%) whereas patients in CON attended all three visits.No injuries or adverse effects were reported during the intervention.No changes were detected in habitual physical activity, eating habits, CCS score and medication use throughout the study.

Main findings
The present randomized controlled trial pointed to investigate the efficacy of a 3-month HBCT on numerous indicators related to KOA, cardiometabolic health, as well as mental health among individuals with overweight/obesity, T2DM and KOA.To our knowledge, this is the first pragmatic study evaluating the effects of such a home-based exercise protocol in this cohort.The current results indicated that an injury-free HBCT program meaningfully improved BMI, blood lipid profile, FBG, liver function, musculoskeletal fitness and HRQoL.
Despite the general recommendation of rehabilitation as a primary treatment for KOA, there is inconsistency in the standard approach to therapy programs.According to a study by Nguyen, Lefevre-Colau [51] focusing on the effectiveness and safety of strength training and exercise therapy, rehabilitation is widely advised and considered a crucial treatment for KOA.However, a gap needs to be addressed in improving the reasons for prescribing exercise.One promising approach to maximize the benefits of exercise is CT, which enhances cardiorespiratory and muscular fitness.CT can be advantageous for various chronic conditions, including KOA, as it involves repeatedly performing a series of exercises with minimal or no rest intervals [32].It integrates muscle-strengthening exercises and bodyweight movements into a circuit fashion, aiming to maintain an elevated heart rate throughout the workout [33,34].CT may offer superior advantages compared to traditional aerobic exercise [35,36].Moreover, the relatively brief period allocated to each activity in cognitive therapy creates an environment that is favorable for group engagement, promoting enhanced commitment and cooperation among the individuals involved [32,33,36,52].Lowering body fat has been demonstrated as a positive outcome of CT, contributing to improved Table 3 Pairwise comparisons between HBCT and CON in time for BMI, musculoskeletal fitness, and HRQoL.body composition [53].The CT has the potential to more effectively stimulate the breakdown of fat tissue (lipolysis) compared to traditional aerobic training [54,55].

Blood lipids
In terms of the improvements in lipid homeostasis, the present outcomes are consistent with those reported in previous studies investigating CART in lipid homeostasis [56][57][58][59][60][61].The beneficial changes in the lipid profile after exercise could be due to the involvement of larger muscle mass in CT.This could have caused a greater reduction in intramyocytic fat content and increased fatty acid oxidation capacity compared to CON.These positive effects may have caused an increase in the clearance of lipids from circulation [62,63].Physical exercise can increase the expression of PPAR and PGC-1 messenger RNAs, leading to improved metabolic flexibility and energy utilization in both muscle and adipose (fat) tissue as reported by a previous study [64].In addition, the improvement in lipid metabolism following an exercise intervention may suggest enhanced cardiovascular health, as exercise is known to positively impact lipid levels by reducing LDL-C and increasing HDL-C.This particular improvement could potentially lower the risk of cardiovascular complications; however, the exact mechanism behind these changes in lipids is unknown, and thus further research is needed in this area [65].Also, a recent meta-analysis examined the effect of aerobic and resistance training on lipid profiles in people with T2DM [66].The findings of the included studies were varied, with two claiming that exercise had no impact on LDL-C, HDL-C, TC, or TG [67,68], and one study reported exercise lower TC and altered HDL-C and LDL-C levels [69].Other studies have shown a significant reduction in TG [70][71][72] and TC [73][74][75][76][77]; however no difference in LDL-c and HDL-c was found following combined aerobic and resistance training [74,75].The conflicts between these findings may be explained by the difference in the exercise intensity, volume and the baseline participants' values, which were not significantly changed after the exercise intervention [58].

Liver function
In the present study, liver function parameters showed exceptional reductions in HBCT compared to CON, indicating that exercise improved blood flow to the liver, decreased liver inflammation, reduced fat in the liver, and reduced whole-body fat [78,79].Exercise increases blood flow throughout the body, including the liver [80], and therefore this enhanced blood flow delivers oxygen and nutrients to the liver, facilitating its metabolic processes and supporting overall liver health [81].Improved oxygenation and nutrient supply can reduce liver injury and normalize ALT and AST levels [82].In line with our study, Słomko, Zalewska [83] conducted a systematic review and meta-analysis of 15 RCTs involving 740 patients with metabolic-associated fatty liver disease; most of the included studies involved overweight and obese patients with underlying T2DM.It was found that all types of aerobic exercise protocols significantly decreased ALT levels and improved the metabolically associated fatty liver disease compared with the control group [84].On the other hand, other study found no significant difference in liver function after the intervention [85].However, it is worth noting that the extent of improvement may vary depending on factors, such as the baseline liver function, exercise intensity, and duration as well as the overall lifestyle habits of the patients.

Glucose control
In the current study, we found a significant decrease in FBG in the intervention group, which is in accordance with previous studies that conducted a combination of aerobic and resistance training [61,71,73,[86][87][88][89][90][91][92].This finding could be attributed to the improvement of insulin-stimulated glucose transport in skeletal muscle and increased tissue exposure to insulin and glucose [93][94][95][96].In other studies, overweight and sedentary patients with underlying T2DM have shown an improvement in insulin action after 4 to 8 months of physical training [97,98].The observed enhancement in the glucose tolerance in the T2DM patients in the intervention group could be due to an increase in the glucose clearance rate associated with an increase in muscle blood flow as well as an improvement in the body's capacity to absorb glucose [99].In contrast, a previous study of elderly patients with T2DM did not find any change in FBG after 16 weeks of combined aerobic and resistance training [99].
Other studies reported no difference in FBG following the exercise [74,75].The inconsistencies in these studies compared to the present study could be due to the physiological complexity involved, the small sample size, and the variations in exercise training procedures.

Anthropometry
As for BMI, significant reductions were detected in HBCT which is in line with previous studies [71,73], suggesting that exercise increases energy expenditure resulting in a calorie deficit and contributing to weight loss.A similar finding was also found in a study that demonstrated a substantial decrease in BMI after six months of home-based combined aerobic and resistance training among T2DM patients [100].This finding may be attributed to the HBCT as well as methodological considerations, high levels of compliance and retention among the participants [58,74,87,[100][101][102][103].Furthermore, it is unlikely that any changes in diet or exercise routines that existed independent of the intervention had an influence on our results.In the present study, no changes in dietary patterns or outside-of-the-study physical activity were found in the participants' logbook, which was evaluated at each visit.

Musculoskeletal fitness
Concerning musculoskeletal fitness indices, the scores for 30CST and TUG demonstrated significant elevations following HBCT that combined aerobic and resistance training consistent with previous studies in patients with T2DM [14,73,88,91,104,105].This finding implies that exercise may improve muscular fitness and functional capacity in KOA patients.Contrastingly, another study failed to identify a notable difference in TUG performance [106].Similarly, a recent systematic review and meta-analysis revealed the absence of significant improvements in functional performance based on 30CST and TUG scores [107].This discrepancy may be ascribed to variations in participants' baseline fitness levels, inadequate intervention duration to provoke discernible changes, potential methodological constraints, or the necessity for more specific and targeted exercise interventions.In general, positive musculoskeletal adaptations to CT-like programs are critical for this cohort, since people with excessive weight, impaired glucose metabolism and KOA are very likely to experience poor functionality, numerous physical limitations and limited independence when performing activities of daily living [108,109].Hence, time-efficient, integrated exercise training solutions may be important tools for inducing noticeable improvements in muscular fitness, flexibility, mobility, agility, dynamic balance and functionality as previously reported [23,26].

Health-related quality of life
Regarding alterations in Health-Related Quality of Life HRQoL, meaningful enhancements were observed in specific dimensions related to KOA.More specifically, the physical activity function and pain scores for HBCT were similar to previous studies [14,91].These findings could be possibly due to the improvement in muscular strength which might likely decrease knee pain and improve walking ability, which subsequently, improves the HRQoL of the patients in the current study.Another research recruiting elderly T2DM patients reported that 16 weeks of combined aerobic and resistance training improved both walking capacity and HRQoL [99].The present improvements in HRQoL, musculoskeletal fitness, and pain among patients with overweight/ obesity, T2DM and KOA following HBCT may support the prescribed training structure and configuration that combine aerobic-and resistance-based activities for enhancing both cardiorespiratory and neuromuscular conditioning in a time-efficient manner.This is certainly relevant for people with T2DM who have comorbidities that might restrict traditional gym-based exercise circuits or who do not feel comfortable in a gym and/or hospital environment.

Pain
Regarding the pain score, a significant improvement was noted in HBCT compared to CON.This finding could be possibly due to the improvement observed in lower body muscular strength and endurance, functionality, and mobility following the exercise intervention.Such an observation underlines the key role of exercise in lowering pain, increasing range of motion and flexibility as well as strengthening the knee joint muscles.In agreement with our study, a recent systematic review and metaanalysis incorporated seven trials with 346 patients diagnosed with KOA, revealing a significant reduction in the pain score following a CT program [107].

Comorbidity
However, comorbidity can pose additional difficulties in implementing exercise therapy for KOA patients [110].
According to the previous study, it was found that the presence of comorbidities has major effects on the prognosis [111] and may affect treatments; thus, it should be taken into concertation [112].Unfortunately, no evidence-supported method is available for treating individuals with both KOA and additional health conditions [113].The current KOA guidelines do not provide specific recommendations for exercise adaptations related to comorbidities [114][115][116].In certain cases, merging multiple treatment plans for different diseases may be infeasible because a particular therapy could interfere with the normal progression of a coexisting condition or have adverse interactions with another medication [117].Moreover, exercise is rarely recommended for elderly individuals with KOA and serious underlying comorbidities.They frequently discontinue the treatment or receive inadequate care as therapists may reduce the intensity of the exercise to an insufficient level.Consequently, no evidence-based exercise regimen is ideal for managing overweight individuals with KOA and T2DM.Therefore, the present study provides important insights into the positive role of a real-world exercise solution, integrating cardiorespiratory and neuromuscular stimulus into a single, time-efficient session for a cohort representing the vast majority of adults in the Western world [118].

Strengths and limitations
The current findings cannot be generalized to people of other ethnic groups, ages, and BMI ranges.Nevertheless, the recruitment of older adults with impaired cardiometabolic and musculoskeletal health aims to represent an important cohort.In addition, this randomized controlled trial did not examine various cardiovascular risk factors associated with metabolic dysregulation, such as resting blood pressure, glucose homeostasis, redox status, and cardiorespiratory fitness.However, the conduction of a pragmatic study in an unsupervised, homebased setting during the COVID-19 pandemic may provide insights into time-efficient and feasible exercise approaches under real conditions for people demonstrating insufficient physical activity levels while being impacted by the most common lifestyle-related chronic diseases.Furthermore, the lack of additional psychometrics, such as exercise enjoyment and affective valence did not provide data related to the potential association between pleasure and high adherence (98.6%) and attendance (91.7%) rates, which were relatively high in comparison to the earlier studies [70,71,88,91,92,119], especially since 80% of patient retention at the end of the intervention was considered to be very high [120,121].Also, the dose-response effects investigation between HBCT and various physiological, psychological, biochemical and hormonal indicators among people with overweight/obesity, KOA and T2DM may be an important direction in a future research attempt in this area as previously articulated [38].Finally, the lack of a reliable and valid questionnaire assessing physical activity and caloric intake is an additional limitation, since only selfreport information was collected through an interview in order to ensure that participants did not change their habits throughout the intervention.

Conclusion
The findings from our study demonstrate compelling improvements in lipid profiles, musculoskeletal fitness, and OA-related QoL among overweight or obese older adults with T2DM and KOA following a 3-month HBCT.Our pragmatic approach highlights significant reductions in TC, TG, LDL-C, aminotransferase levels, alanine aminotransferase, FBG, and knee pain.Notably, HBCT also led to meaningful increases in HDL-C, lower body muscular strength, endurance, functional capacity, mobility, and HRQoL.These outcomes underscore the potential public health impact of a practical, injury-free exercise solution integrating bodyweight and resistancebased activities in a home-based setting.Our results suggest that HBCT may serve as a supplementary real-world exercise strategy for individuals characterised by sedentary lifestyles, excess weight, and metabolic dysregulation, such as those with T2DM and KOA.In summary, the targeted improvements observed in lipid metabolism, musculoskeletal health, and overall well-being among this at-risk population demonstrate the efficacy and feasibility of HBCT as an accessible and impactful exercise approach.These findings provide valuable insights for medical and exercise professionals seeking Fig 1 illustrates the CONSORT flow diagram of the study.

Fig. 1
Fig. 1 Consort flow diagram of the study

Table 2
Pairwise comparisons between HBCT and CON in time for biomarkers